A number of different stem cells, including embryonic, bone marrow and cardiac progenitors, are currently being examined as potential therapies to repair injured tissues, for example myocardium. These approaches typically focus on regenerating cellularity and restoring tissue function. Thus far, independent of the particular cell type, stem cell therapies have consistently demonstrated enhancements in tissue function in experimental models and clinical trials. However, the precise mechanisms responsible for global functional improvements have yet to be fully elucidated since improvements can be detected even in the absence of any substantial amount of regenerated tissue. This suggests that even if stem cells capable of differentiating into specific cell types are delivered to a damaged tissue, intrinsic signals capable of directing tissue specific differentiation may be absent or deficient within the microenvironment of the damaged tissue.
To date, biomaterials utilized in tissue restoration therapies have largely served a structural role as either a delivery vehicle for tissue and tissue engineering or as a patch for tissue defects. Despite the clear therapeutic potential of stem cells, several drawbacks, including the potential immunogenicity and tumorigenicity of the cells in vivo still exist.
The extracellular matrix (ECM), largely composed of adhesive proteins, cytokines and polysaccharides, constitutes the biochemical and mechanical nature of the microenvironment that regulates cell fate and function within tissues. Curiously, very little is known about the complex assembly of the ECM present during early cell and tissue development though these molecules are thought to provide critical cues that instruct cell behavior. Pluripotent ES cells provide an in vitro model of development and are currently being examined in a number of experimental models as a potential cell therapy to regenerate diseased or injured tissues. However, thus far, no studies have examined the role of the extracellular matrix contributed by ES cells to tissue repair processes.
It is an object of the present invention to provide acellularized biomaterial derived from pluripotent cells, for example embryonic stem cells.
It is also an object of the present invention to provide methods and compositions that promote wound healing, promote tissue regeneration, or reduce scarring.